This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims to my project have changed from the inception of this program due to new and exciting findings generated in our laboratory that point to the identification of a novel co-stimulatory pathway in tumor specific cytotoxic T-lymphocytes (CTL). Our published and preliminary data indicate that T-lymphocytes express functional Toll-like receptors. For instance, CTLs show a preferential expansion over TLR2[unreadable]/[unreadable]OT-1 CTLs when adoptively transferred into the same recipient followed by injection with TLR1/2 ligand and antigen. The hypothesis underlying this grant is that the engagement of TLR2 on CTLs in vivo augments clonal expansion, facilitates memory development, and potentiates their functional capacity. The main objectives are to 1) achieve a mechanistic understanding of how TLR2 engagement on CTLs enhances clonal expansion and memory development and 2) determine the molecular mechanisms through which TLR2 engagement on CTLs augments the expression of effector molecules resulting in enhanced anti-tumor activity. These studies will help identify novel co-stimulatory pathways, thereby providing opportunities for increasing the efficiency with which tumor-specific effector and memory cells are generated and boosting cytolytic activity by manipulating TLR signaling in CTLs.